Sleep Macrostructure, Cyclic Alternating Pattern and <scp>CSF</scp> Cytokines in De Novo Relapsing–Remitting Multiple Sclerosis: A Controlled Polysomnographic Study

Multiple sclerosis is frequently associated with sleep disorders. This study aimed to evaluate subjective and objective sleep parameters in de novo relapsing-remitting multiple sclerosis patients compared to healthy controls and to explore correlations with cerebrospinal fluid cytokines. Twenty-one patients underwent CSF cytokine analysis, overnight polysomnography and sleep quality assessments; 21 HCs also participated in sleep evaluations. We analysed sleep macrostructure and the cyclic alternating pattern. Compared to controls, patients exhibited increased sleep period time, time in bed, REM sleep latency, N3 sleep percentage and wakefulness after sleep onset, along with reduced sleep efficiency and REM sleep percentage. These alterations were more pronounced in patients who also had obstructive sleep apnoea. Cyclic alternating pattern analysis revealed increased CAP time and rate-particularly higher A3 indices and duration of A phases-suggesting enhanced sleep fragmentation. A significant association was found between IL-1β and longer Phase B duration, and IL-15 showed a positive correlation with A3 mean duration in the cyclic alternating pattern, indicating inflammatory modulation of sleep architecture. Fatigue was negatively correlated with A1 mean duration and cycle mean duration. These findings demonstrate that de novo relapsing-remitting multiple sclerosis is associated with significant sleep fragmentation, particularly in patients with obstructive sleep apnoea and suggest that pro-inflammatory cytokines might influence sleep homeostasis through adaptive mechanisms. This underscores the importance of addressing sleep quality in multiple sclerosis management.